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Lecture 6Web: pollev.com/ucibioText: To: 37607Type in: 169964 1Folding proteinsNeed precise shape active siteAmino acid sequence determines foldingSecondary structural elements form2Motifs & DomainsMotif: ______________________ Eg. Helix-turn-helixWill not fold independently

3Motifs & DomainsDomain:________________Eg. Ig domainFolds independently

4Working togetherQuaternary structureMultiple peptide chains interactStructure & function dependent on interactions5Quaternary structure

6Another protein folding experimentAPXNormal activity250 units450 units+Heat5 units9 units+Heat +recovery188 units14 units+Protein Y244 units412 units+Y + heat7 units11 units+heat +Y +recovery198 units388 units7Another protein folding experimentTWO Sentences on ConclusionsUpload into Bio98 Folding exptMidnight tonight8How do proteins find the right conformation?Every conformation = Gazillion years!Sequential stabilization of intermediatesWe DONT KNOW tons!9Sequential stabilization of intermediates

http://www.youtube.com/watch?v=YANAso8Jxrk10Protein folding: Another view

http://www.youtube.com/watch?v=sD6vyfTtE4U11The importance of structureWhy determine structure?Structure = FunctionMechanism of functionRational drug design12The importance of protein structureChaperones & protein foldingMisfolded proteins are very, very bad!E.g. Huntingtons disease13Aggregation of mutant HuntingtonsTag protein - GFPPut tagged proteins in cellsCompare: - Normal - Mutant

14The importance of structureChaperones & protein foldingMisfolded proteins are very, very bad!E.g. Huntingtons diseaseE.g. Prions15